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To understand the need for animal studies To know the advantages and disadvantages of animal studies To know which

ch animals are routinely used for animal studies Rules and ethics regarding animal research Important animal studies in orthodontics

Research is the corner stone for development in medical and dental science Scientists need to study natural situations to understand life processes and to investigate how introducing a particular substance can change living systems. There are several tiers of research and not all studies can be carried out on human body due to safety and ethical concerns

The processes in any organism are far more complicated than just the sum of the individual parts.
It is difficult to replicate at the lab bench the complex interactions.

Animals and humans are very similar; we have the same organ systems performing the same tasks in more or less the same way. Animals suffer from diseases similar to humans; like cancers, TB, flu and asthma.

YEAR 1796 1881 1902 1921 1933 1939 1954 1956 1964 1982 1990 1997 2000

MEDICAL ADVANCEMENT
Smallpox vaccine developed Anthrax vaccine developed Lifecyle of Malaria discovered Insulin discovered Tetanus vaccine developed Anticoagulants developed Polio vaccine developed Open-heart surgery & pacemakers developed Cholesterol regulation discovered Leprosy treatment developed Organ transplant techniques advanced Prions discovered & characterized Brain signal transduction discovered

ANIMAL CREDITED
Cow Sheep Pigeon Dog, Fish Horse Cat Mouse, Monkey Dog Rat Armadillo Dog, Pig, Sheep, Cow Hamster, Mouse Sea Slug, Mouse, Rat

Foundation for Biomedical Research - 2003

Each species in the animal kingdom is unique. But there are both differences and similarities between animals and humans. This is what comparative medicine is about: researchers use both similarities and differences to gain insight into the many complex human biological systems. Researchers work with animal models that have biological systems similar to that of a human.

For instance, swine and humans share similar cardiovascular and skin systems.

We share 95% of our genes with a mouse, making them an effective model for the human body. Organisms that look very different can be very similar genetically. Chimpanzees share 98.7% of their DNA with humans. Zebrafish share 75 - 80% of their DNA with humans.

The differences exhibited in a research model can also provide great insights. For instance, sharks rarely get cancer, cockroaches can regenerate damaged nerves, and some amphibians can regrow lost limbs. By studying these animals we may learn how they accomplish these remarkable feats and apply the principles to human medicine.

rat
Guinea pig sheep

Zebra fish dog

armadillo

rabbit
ferret pig

81% 18%

Rats, mice and other rodent

Fish, amphibians, reptiles and birds


Small mammals, mostly rabbits and ferrets Sheep, cows, pigs and other large mammals Dogs and cats Primates, mainly macaque monkeys

0.8%
0.4% 0.12%

0.07%

Study aspect 1. 2. 3. growth Genetics Histo-chemistry

animal Mice Mice Rodents, dogs

4
5. 6.

Condylar changes
Implants Distraction osteogenesis

rodents
Dogs Dog

7.

Surgical procedures

dog

Areas of research

Mice and rats are the most commonly used animals for genetic studies. They may be used in basic research to discover the function of a particular gene in embryonic development (or the ageing of cells), or in the study of diseases.

Genetically altered (GA) Genetically modified (GM) Transgenic Knockout

Genetically modified organisms as those which have been genetically changed. Genetically altered organisms include both GM organisms and those carrying 'natural' mutations.

Transgenic refers to a subtype of GM animals whose genomes have been altered by the insertion of part of DNA from another organism. A knockout animal has had one or more genes inactivated or silenced.

Most accurate way to understand the effects of any substance or procedure on a living body.

Easy to mimic interactions at organ system level. Helps researchers find newer drugs and treatments Human harm is reduced and human lives are saved but also animal lives are saved because of animal testing.

Animals may not have the exact same physiology as humans but animal testing is accurate enough to test whether a substance is even safe enough for human trials. Studies requiring sacrifice can be performed
Alternative methods of testing do not simulate humans in the same way

- High cost : The housing , feeding, carrying treatments, controlling the environment, is very expensive. Animals used for testing are usually obtained from specific breeding facilities and come with a high price tag. - Morality : Animals have the right to live their own life; and we must not meddle with them just because we can.

-Necessity/validity :

It is not important enough to sacrifice an animal, like testing the effect of cosmetics and household products.
-Usefulness : Animals kept in unnatural conditions (a lab and not their natural habitat), or animals in pain or distress, are not giving rise to accurate or consistent results. Humans are quite different from other animals so the reaction of the drug in the animals body versus the human body is different.

Replace the use of animals with alternative techniques. Reduce the number of animals used to a minimum, to obtain
information from fewer animals or more information from the same number of animals.

Refine the way experiments are carried out, to make sure


animals suffer as little as possible. This includes better housing and improvements to procedures which minimize pain and suffering and/or improve animal welfare.

Guidelines have been laid down by the INDIAN NATIONAL SCIENCE ACADEMY: Animal experiments should be undertaken only after due consideration of their relevance for human or animal health. The animals selected should be of an appropriate species and quality. Minimum number should be used to obtain scientifically and statistically valid results.
Experiments on Animals ( Control and Supervision ) Rules, 1968

Investigators should treat animals with kindness and avoid discomfort, distress or pain.
Appropriate sedation, analgesia or anaesthesia must be given to avoid discomfort. The best possible living condition should be provided to animals used for research. Care of animals should be under the supervision of a veterinarian.

The experiment should not be performed for the purpose of attaining or retaining manual skill.
In-vitro systems to replace or reduce the number of animals should be used wherever possible.

1. In vitro studies 2. Tests using cell or organ cultures rather than whole organisms 3. organisms such as worms or bacteria are used instead of mammals. 4. Computer models to predict outcomes of testing.

However, each of these methods provides limited information that applies to a very specific test situation and may not fully anticipate the results in a complicated organism (such as humans) with many interacting organ systems.

Lei Sun; Meiqing Wang; Jianjun He; Lei Liu; Shuang Chen; Sven E. Widmalm Angle Orthod. 2009;79:5153.

Twenty-four 8-week-old rats divided into a control group (left untreated) and an experimental group where a non-balanced occlusion was created.
Elastic rubber bands, were inserted and 1 week later were replaced by plastic material between the rst and the second molars of the left maxillary and the right mandibular dentitions to move the rst molars about 0.8 mm mesially. This created and maintained a physiologically nonbalanced occlusion. The animals were euthanized 8 weeks later, and the TMJ disc thickness was measured histologically

Results: The intermediate zone was thicker in the experimental group than in the control group but no differences were found between groups regarding the anterior and posterior bands. There were no signicant sex-related effects on this observation. The results indicate that the intermediate zone of rat TMJ disc has the ability to adapt to the alteration of the space between condyle and fossa caused by occlusion changes.

Yehya Ahmed Mostafa, Ahmed Mostafa Heider Mona Mohamed Salah Fayed, Samah Mehanni, Nader Nabil ElBokle

Am J Orthod Dentofacial Orthop 2009;136:570-7

Aim: (1) to identify the effect of the Corticotomy on orthodontic tooth movement compared with the standard technique (2) explore the histologic basis of the difference between the 2 techniques. Methods: Six dogs, aged 6 to 9 months, were used in this study. Extraction of the maxillary second premolar and miniscrew placement were done bilaterally in the maxilla

On the right side, the corticotomy was performed. The rst premolars were distalized against the miniscrews with nickel-titanium coil springs on both sides. One dog was killed each week after orthodontic force application.

Results: The rst premolar on the CF side moved signicantly more rapidly (P \0.05). Histologic ndings showed more active and extensive bone remodeling in the CF group.
Conclusions: The CF technique doubled the rate of orthodontic tooth movement. The acceleration of tooth movement associated with corticotomy is due to increased bone turnover and based on a regional acceleratory phenomenon.

Colin K. L. Ong, ; Laurence J. Walsh, ; Aart A. R. Taverne, Anne L. Symons, (Angle Orthod 2000;70:118125.)

This study examined the effect of prednisolone on orthodontic movement using an established rat model.

The corticosteroid treated group (N = 6) was administered prednisolone (1 mg/kg) daily, for a 12-day; the control group (N = 6) received equivalent volumes of saline.
On day 12, an orthodontic appliance was placed which exerted 30 g of mesial force to the maxillary rst molar. Animals were sacriced on day 24 and tooth movement was measured.

There were no signicant differences in the magnitude of tooth movement between the 2 groups.
steroid-treated rats displayed less root resorption on the compression side and fewer TRAP-positive cells within the PDL space on the same side. This suggests steroid treatment suppressed clastic activity.

Angle Orthodontist, Vol 78, No 1, 2008

AIM : To associate the expressions of SOX9 and type II collagen during growth in the synchondrosis with and without tensile stress in order to understand the role of these factors in the growth of cartilage in spheno-occipital synchondrosis.

Materials and Methods: Sixty 1-day-old male BALB/c mice were divided into experimental and control groups.

Each group was subdivided again into ve different time points which were 6, 24, 48, 72, and 168 hours.

Each mouse was sacriced using an overdose of pentobarbitone sodium.


The synchondroses were aseptically removed and incubated in a 24-well plate with or without tensile stress in tissue culture. Tissue sections were stained immunohistochemically to quantitatively analyze the expression of SOX9 and type II collagen.

Results: There was a statistically signicant increase of 57% in the expression of SOX9 between the experimental and control groups at 24 hours, followed by a signicant increase of 44.4% in the expression of type II collagen at 72 hours. Conclusions: SOX9 may play an important role for early differentiation of chondrocytes and increase the expression of type II collagen, a major component of the extracellular matrix, during the growth of cartilage in the spheno-occipital synchondrosis.

Angle Orthodontist, Vol 78, No 1, 2008

Objective: The aim of this study is to examine the effect of gene therapy (specic vascular growth inducting genes )on condylar growth by means of a morphological assessment. Materials and Methods: Ninety 35-day-old female rats were randomly divided into three groups, which received any of the injections of recombinant adenoassociated virus mediated vascular endothelial growth factor (rAAVVEGF), rAAV mediated enhanced green uorescence protein (rAAVeGFP), or phosphate-buffered saline (PBS) into both mandibular condyles.

Each group of rats was sacriced on the following experimental days: 7, 14, 21, 30, and 60. Left halves of the mandibles were isolated and digital pictures were obtained.

Results: The length of condylar process as well as mandibular length signicantly increased on day 30 and continued to increase until the end of the experiment. The width of condyle increased signicantly from day 30 and lasted to day 60. Condylar length was found to be signicantly longer on day 60.

Conclusion: Gene therapy with VEGF stimulates condylar growth at will. The rAAV-VEGF is an excellent candidate for future gene therapy to induce mandibular growth

A. Bakr M. Rabie, Zhihe Zhao, Gang Shen, Urban Hgg, Wayne Robinson
Am J Orthod Dentofacial Orthop 2001;119:390-400

AIM: To identify the sequence of cellular changes in the glenoid fossa and to quantify the amount of bone formation in response to mandibular advancement. MATERIAL AND METHOD: One hundred 35-day-old rats were randomly divided into 5 experimental groups (15 rats each) and 5 control groups (5 rats each).

In the experimental groups, functional appliances were used to create continuous forward mandibular advancement. The rats were killed after 3, 7, 14, 21, and 30 days. Sections were cut through the glenoid fossa in the parasagittal plane and stained with periodic acid and Schiffs reagent for evaluation of bone formation and with hematoxylin and eosin for observation of cellular response. RESULT: In the control rats, bone formation decreased over time in all regions. In the experimental group, bone formation significantly increased from day 7 to day 30. Day 21 marked the highest levels of bone formation.

CONCLUSION: Mandibular protrusion resulted in the osteoprogenitor cells being oriented in the direction of the pull of the posterior fibers of the disc and also resulted in a considerable increase in bone formation in the glenoid fossa.

Although research on animals is an indispensible part of medical/dental research; indiscriminate use of animals must be avoided.
Research carried out in accordance with the principles laid down by the governing bodies can reduce the pain and discomfort to animals.

Anti-hypertensive medicines ACE inhibitor was developed due to research into the Brazilian pit viper venom . Animal research contributes to 70% of the Nobel prizes for physiology and medicine. Monkeys are used to develop and test HIV medicines because the virus does not infect small animals like mice and rats.

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